It has previously been shown in our laboratory that high pressure vesico-ureteral reflux (VUR) of uninfected urine produces fibrosis; (a) focally throughout the renal parenchyma, (b) in the perivascular spaces, (c) in the capsule and (d) in the perirenal tissues, outside the renal sinus and around the calicine and pelvic walls. These changes were observed in different stages of evolution in 8 previous uninfected animals, at least one of which developed severe hypertension. We wish to expand this work in much greater detail because of the documented cases of children with VUR, renal scarring and severe hypertension in whom there is no history of infection. Particularly we wish to answer the following questions: (1) Is there any evidence that it is urine itself which gives rise to this fibrosis? (2) What are the pathways by which urine reaches the above sites of fibrosis? (3) Is the hypertension related to the renin-angiotension mechanism? (4) Do intrinsic arterial wall damages develop in this model? Artificial VUR will be induced in piglets by incising the ureteral orifices and high pressure VUR produced by temporary, progressive, urethral constriction. It is known that under these circumstances the bladder contents are forced retrogradely into the kidney and out again via the lymphatics. We will determine the pathways used (a) by the injection of a dye - Barium sulfphate mixture into the bladder and observing its pathways within and out of the kidney at necropsy, (b) by using Tamm-Horsfall protein (THP) as a marker for urine and detecting its distribution by an immunofluorescent technique, and (c) Investigating the immunologic response to THP and other urinary constituents in this model. The activation of the renin-angiotension system will be assessed: (1) by the effect of an in vivo intravenous infusion of Saralasin on blood pressure and plasma renin levels; (2) by histopathologic evidence of juxtaglomerular body hyperplasia and an excess of renin-producing intracellular granules. Fibrosis and arterial wall changes will be assessed by microscopy